US9949919B2ActiveUtilityA1

Stable, non-irritating topical formulations of hydroquinone

Assignee: SHAMROC INCPriority: Feb 27, 2013Filed: Jun 23, 2015Granted: Apr 24, 2018
Est. expiryFeb 27, 2033(~6.6 yrs left)· nominal 20-yr term from priority
A61K 8/64A61K 2800/75A61K 8/4946A61K 8/675A61Q 19/00A61K 8/9789A61K 8/347A61K 8/36A61K 8/602A61Q 19/02A61K 8/342A61K 8/9706A61K 8/494A61K 8/9794A61K 8/345A61K 8/42A61K 8/498A61K 8/97
70
PatentIndex Score
1
Cited by
7
References
12
Claims

Abstract

Described herein are methods and compositions for increasing the efficacy and decreasing the irritancy of topical formulations of hydroquinone.

Claims

exact text as granted — not AI-modified
We claim: 
     
       1. A method for decreasing the irritancy of a 1%-3% hydroquinone-containing formulation comprising adding an emollient and an anti-irritant to the formulation, wherein the formulation comprises an oil-in-water emulsion, thereby forming a less irritating hydroquinone-containing formulation, wherein the less irritating hydroquinone-containing formulations consists essentially of, by weight of the formulation 
       
         
           
                 
                 
               
                     
                 
                   Purified Water 
                   From about 30% to about 70% 
                 
                   Hydrofluorocarbon 227ea 
                   From about 6% to about 18% 
                 
                   Pentylene Glycol 
                   From about 3% to about 7% 
                 
                   Cyclomethicone 
                   From about 3% to about 7% 
                 
                   Niacinamide 
                   From about 2% to about 6% 
                 
                   Isononyl Isononoate 
                   From about 1% to about 4% 
                 
                   C 12 -C 15  Alkyl Ethylhexanoate 
                   From about 1% to about 4% 
                 
                   Glycerin 
                   From about 1% to about 3% 
                 
                   Hydroquinone 
                   From about 1% to about 3% 
                 
                   Alpha-Arbutin 
                   From about 1% to about 3% 
                 
                   Dimethicone/Divinyldimethicone/ 
                   From about 1% to about 3% 
                 
                   Silsesquioxane Crosspolymer 
                     
                 
                     Moringa Oleifera  Seed Oil 
                   From about 1% to about 3% 
                 
                   Glyceryl Stearate 
                   From about 1% to about 3% 
                 
                   Cetyl Alcohol 
                   From about 1% to about 3% 
                 
                   Dimethicone 
                   From about 0.5% to about 1.5% 
                 
                   Cetearyl Alcohol 
                   From about 0.5% to about 1.5% 
                 
                   Kojic Acid 
                   From about 0.5% to about 1.5% 
                 
                   Panthenol 
                   From about 0.5% to about 1.5% 
                 
                   1-Methylhydantoine-2-Imide 
                   From about 0.5% to about 1.5% 
                 
                   Algae Extract and Mugwort 
                   From about 0.5% to about 1.5% 
                 
                   ( Artemisia vulgaris ) Extract 
                     
                 
                   Magnesium Aluminum Silicate 
                   From about 0.5% to about 1.5% 
                 
                   PEG- 75 Stearate 
                   From about 0.5% to about 1.5% 
                 
                     Avena Sativa  (Oat) Kernel Extract 
                   From about 0.1% to about 1.0% 
                 
                   Saccharomyces/ Xylinum /Black Tea 
                   From about 0.2% to about 0.6% 
                 
                   Ferment 
                     
                 
                     Palmaria Palmata  Extract 
                   From about 0.1% to about 0.4% 
                 
                     Brassica Napus  Extract 
                   From about 0.3% to about 1.0% 
                 
                     Punica Granatum  (Pomegranate) 
                   From about 0.1% to about 0.4% 
                 
                   Seed Oil 
                     
                 
                     Rubus Occidentalis  (Black 
                   From about 0.1% to about 0.4% 
                 
                   Raspberry) Seed Oil 
                     
                 
                   
                     Vaccinium Macrocarpon 
                   
                   From about 0.1% to about 0.4% 
                 
                   (Cranberry) Seed Oil 
                     
                 
                     Citrullus Lanatus  (Watermelon) 
                   From about 0.01% to about 0.05% 
                 
                   Seed Oil 
                     
                 
                     Rubus Idaeus  (Raspberry) Seed Oil 
                   From about 0.01% to about 0.05% 
                 
                     Salvia Hispanica  (Chia) Seed Oil 
                   From about 0.01% to about 0.05% 
                 
                   Tetrahexadecyl Ascorbate 
                   From about 0.3% to about 0.7% 
                 
                   Ceteth-20 
                   From about 0.2% to about 0.6% 
                 
                   Steareth-20 
                   From about 0.2% to about 0.6% 
                 
                   Allantoin 
                   From about 0.3% to about 0.7% 
                 
                   Chlorphenesin 
                   From about 0.1% to about 0.4% 
                 
                   Hexapeptide-2 
                   From about 0.1% to about 1.0% 
                 
                   Jojoba Esters 
                   From about 0.1% to about 0.4% 
                 
                     Moringa  Oil/Hydrogenated Moringa  
                   From about 0.1% to about 0.4% 
                 
                   Oil Esters 
                     
                 
                   Bisabolol 
                   From about 0.1% to about 0.3% 
                 
                   Fragrance 
                   From about 0.1% to about 0.3% 
                 
                   Sodium Bisulfite 
                   From about 0.02% to about 0.07% 
                 
                   Sodium Sulfite 
                   From about 0.02% to about 0.07% 
                 
                   Tocopheryl Acetate 
                   From about 0.05% to about 0.15% 
                 
                   Xanthan Gum 
                   From about 0.05% to about 0.15% 
                 
                   Citric Acid 
                   From about 0.1% to about 0.3% 
                 
                   Potassium Sorbate 
                   From about 0.1% to about 0.3% 
                 
                   Sodium Benzoate 
                   From about 0.1% to about 0.3% 
                 
                   Dextran 
                   From about 0.1% to about 1.0% 
                 
                   Sodium Hyaluronate 
                   From about 0.005% to about 0.015% 
                 
                   BHT 
                   From about 0.1% to about 0.3% 
                 
                   Stearyl Glycyrrhetinate 
                   From about 0.05% to about 0.15% 
                 
                   Disodium EDTA 
                   From about 0.05% to about 0.15% 
                 
                   Phenoxyethanol 
                   From about 0.01% to about 0.10% 
                 
                   Hydroxvethylcellulose 
                   From about 0.1% to about 1.0% 
                 
                     Glycyrrhiza Glabra  (Licorice) 
                   From about 0.02% to about 0.07%. 
                 
                   Root Extract 
                 
                     
                 
             
                
               
               
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
               
            
           
         
       
     
     
       2. The method of  claim 1 , wherein the less irritating hydroquinone-containing formulation, upon application to the skin of an affected subject, does not produce edema or erythema. 
     
     
       3. The method of  claim 1 , wherein the less irritating hydroquinone-containing formulation, upon application to the skin of affected subjects, shows an average reported irritation no more than mild after 4 weeks. 
     
     
       4. The method of  claim 1 , wherein the less irritating hydroquinone-containing formulation, upon application to the skin of affected subjects, no more than 20% of subjects report irritation after 4 weeks. 
     
     
       5. The method of  claim 1 , wherein the less irritating hydroquinone-containing formulation, upon application to the skin of affected subjects, shows an average reported irritation no more than mild after 12 weeks. 
     
     
       6. The method of  claim 1 , wherein the less irritating hydroquinone-containing formulation, upon application to the skin of affected subjects, no more than 16% of subjects report irritation after 12 weeks. 
     
     
       7. A method for decreasing the irritancy of a 1%-3% hydroquinone-containing formulation comprising adding an emollient and an anti-irritant to the formulation, wherein the formulation comprises an oil-in-water emulsion, thereby forming a less irritating hydroquinone-containing formulation, wherein the less irritating hydroquinone-containing formulations consists essentially of, by weight of the formulation 
       
         
           
                 
                 
               
                     
                 
                   Purified Water 
                   From about 30% to about 70% 
                 
                   Hydrofluorocarbon 227ea 
                   From about 6% to about 18% 
                 
                   Pentylene Glycol 
                   From about 3% to about 7% 
                 
                   Cyclomethicone 
                   From about 1% to about 2% 
                 
                   Niacinamide 
                   From about 2% to about 6% 
                 
                   Isononyl Isononoate 
                   From about 1% to about 3% 
                 
                   C12-C15 Alkyl Ethylhexanoate 
                   From about 1% to about 3% 
                 
                   Glycerin 
                   From about 1% to about 3% 
                 
                   Hydroquinone 
                   From about 1% to about 3% 
                 
                   Alpha-Arbutin 
                   From about 1% to about 3% 
                 
                   Dimethicone/Divinyldimethicone/ 
                   From about 1% to about 3% 
                 
                   Silequioxane Crosspolymer 
                     
                 
                   Glyceryl Stearate 
                   From about 1% to about 3% 
                 
                   Cetyl Alcohol 
                   From about 1% to about 3% 
                 
                   Dimethicone 
                   From about 0.5% to about 1.5% 
                 
                   Cetearyl Alcohol 
                   From about 0.5% to about 1.5% 
                 
                   Kojic Acid 
                   From about 0.5% to about 1.5% 
                 
                   Panthenol 
                   From about 0.5% to about 1.5% 
                 
                   1-Methylhydantoine-2-Imide 
                   From about 0.5% to about 1.5% 
                 
                   Algae Extract and Mugwort 
                   From about 0.5% to about 1.5% 
                 
                   ( Artemisia vulgaris ) Extract 
                     
                 
                   Magnesium Aluminum Silicate 
                   From about 0.5% to about 1.5% 
                 
                   PEG- 75 Stearate 
                   From about 0.5% to about 1.5% 
                 
                     Avena Sativa  (Oat) Kernel Extract 
                   From about 0.1% to about 1.0% 
                 
                     Saccharomyces / Xylinum /Black Tea 
                   From about 1% to about 4% 
                 
                   Ferment 
                     
                 
                   Palmaria Palmata Extract 
                   From about 0.1% to about 0.5% 
                 
                     Brassica Napus  Extract 
                   From about 0.04% to about 0.1% 
                 
                     Punica Granatum  (Pomegranate) 
                   From about 0.3% to about 0.9% 
                 
                   Seed Oil 
                     
                 
                     Rubus Occidentalis  (Black 
                   From about 0.3% to about 0.9% 
                 
                   Raspberry) Seed Oil 
                     
                 
                   
                     Vaccinium Macrocarpon 
                   
                   From about 0.3% to about 0.9% 
                 
                   (Cranberry) Seed Oil 
                     
                 
                     Citrullus Lanatus  (Watermelon) 
                   From about 0.06% to about 0.13% 
                 
                   Seed Oil 
                     
                 
                     Rubus Idaeus  (Raspberry) Seed Oil 
                   From about 0.06% to about 0.13% 
                 
                     Salvia Hispanica  (Chia) Seed Oil 
                   From about 0.06% to about 0.13% 
                 
                   Tetrahexadecyl Ascorbate 
                   From about 0.2% to about 0.7% 
                 
                   Ceteth-20 
                   From about 0.1% to about 0.5% 
                 
                   Steareth-20 
                   From about 0.1% to about 0.5% 
                 
                   Allantoin 
                   From about 0.2% to about 0.7% 
                 
                   Chlorphenesin 
                   From about 0.1% to about 0.5% 
                 
                   Hexapeptide-2 
                   From about 0.1% to about 1.0% 
                 
                   Bisabolol 
                   From about 0.1% to about 0.3% 
                 
                   Fragrance 
                   From about 0.1% to about 0.3% 
                 
                   Sodium Bisulfite 
                   From about 0.02% to about 0.07% 
                 
                   Sodium Sulfite 
                   From about 0.02% to about 0.07% 
                 
                   Tocopheryl Acetate 
                   From about 0.2% to about 0.7% 
                 
                   Xanthan Gum 
                   From about 0.05% to about 0.15% 
                 
                   Citric Acid 
                   From about 0.05% to about 0.20% 
                 
                   Potassium Sorbate 
                   From about 0.05% to about 0.20% 
                 
                   Sodium Benzoate 
                   From about 0.05% to about 0.20% 
                 
                   Dextran 
                   From about 0.1% to about 1.0% 
                 
                   Sodium Hyaluronate 
                   From about 0.005% to about 0.015% 
                 
                   BHT 
                   From about 0.1% to about 0.3% 
                 
                   Stearyl Glycyrrhetinate 
                   From about 0.05% to about 0.15% 
                 
                   Disodium EDTA 
                   From about 0.05% to about 0.15% 
                 
                   Phenoxyethanol 
                   From about 0.05% to about 0.1% 
                 
                   Hydroxyethylcellulose 
                   From about 0.1% to about 1.0% 
                 
                     Glycyrrhiza Glabra  (Licorice) 
                   From about 0.02% to about 0.07% 
                 
                   Root Extract 
                     
                 
                     Acacia Decurrens /Jojoba/ 
                   From about 1% to about 3% 
                 
                   Sunflower Seed Wax Polyceryl-3  
                     
                 
                   Esters 
                     
                 
                     Butyrospermum Parkii  (Shea) 
                   From about 1% to about 3%. 
                 
                   Butter 
                 
                     
                 
             
                
               
               
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
               
            
           
         
       
     
     
       8. The method of  claim 7 , wherein the less irritating hydroquinone-containing formulation, upon application to the skin of an affected subject, does not produce edema or erythema. 
     
     
       9. The method of  claim 7 , wherein the less irritating hydroquinone-containing formulation, upon application to the skin of affected subjects, shows an average reported irritation no more than mild after 4 weeks. 
     
     
       10. The method of  claim 7 , wherein the less irritating hydroquinone-containing formulation, upon application to the skin of affected subjects, no more than 20% of subjects report irritation after 4 weeks. 
     
     
       11. The method of  claim 7 , wherein the less irritating hydroquinone-containing formulation, upon application to the skin of affected subjects, shows an average reported irritation no more than mild after 12 weeks. 
     
     
       12. The method of  claim 7 , wherein the less irritating hydroquinone-containing formulation, upon application to the skin of affected subjects, no more than 16% of subjects report irritation after 12 weeks.

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